Time-of-Flight Mass Spectrometer (which will hereinafter be referred to as TOFMS) is a type of device that creates a mass spectrum by measuring the time of flight required for each ion to travel a specific distance and converting the time of flight to the mass-to-charge ratio. This analysis is based on the principle that ions accelerated by a certain amount of energy will fly at different speeds corresponding to their mass. Accordingly, elongating the flight distance of ions is effective for enhancing the mass resolving power. However, elongation of a flight distance along a straight line requires unavoidable enlargement of the device. Given this factor, Multi-Turn Time-of-Flight Mass Spectrometers (which will hereinafter be referred to as MT-TOFMS) have been developed in which ions are made to fly repeatedly along a closed orbit such as a substantially circular shape, substantially elliptical shape, substantially “8” figure shape, or other shapes, in order to simultaneously ensure a long flight distance and achieve the downsizing of the apparatus.
Another type of device developed for the same purpose is the multi-reflection time-of-flight mass analyzer, in which the aforementioned loop orbit is replaced by a reciprocative path in which a reflecting electric field is created to make ions fly back and forth multiple times. Although the multi-turn time-of-flight type and the multi-reflection time-of-flight type use different ion optical systems, they are essentially based on the same principle for improving the mass resolving power and have a common problem, which will be described later. Accordingly, in the context of the present description, the “multi-turn time-of-flight type” should be interpreted as inclusive of the “multi-reflection time-of-flight type”.
As previously described, an MT-TOFMS can provide an elongated flight distance and thereby achieve a high level of mass resolving power. However, it has a drawback due to the fact that the flight path of the ions is a closed orbit. That is, as the number of turns of the ions increases, an ion having a smaller mass-to-charge ratio and hence flying faster overtakes another ion having a larger mass-to-charge ratio and flying at a lower speed. Such an overtaking of the ions having different mass-to-charge ratios results in, on an obtained time-of-flight spectrum, a mixture of peaks originating from the ions having undergone different number of turns. This means it is no longer ensured that the mass-to-charge ratio and the time of flight uniquely correspond In this case, it is impossible to uniquely determine the mass-to-charge ratio of the ions and also their flight distance, so that the time-of-flight spectrum cannot be directly converted to a mass spectrum.
Because of the aforementioned problem, in many conventional MT-TOFMSs, ions are selected in advance (i.e. before they are introduced into the loop orbit) among the ions that originate from a sample generated in an ion source so that their mass-to-charge ratio is assuredly limited to a range where the aforementioned overtaking will not occur. Although a high mass resolving power can be achieved with such a method, the range of the mass spectrum is significantly limited. This is against the advantage of TOFMSs that a mass spectrum with a relatively large mass-to-charge ratio range can be obtained by one measurement.
In the meantime, some methods have been proposed to date for creating a correct mass spectrum from a time-of-flight spectrum obtained by a measurement even in a case where the overtaking of ions occurs while they fly along the orbit, as hereinafter described.
For example, JP-A 2005-79049 (Patent Document 1) discloses a method in which a plurality of time-of-flight spectra for different periods of time of ejection of the ions from the orbit are measured for a target sample and then a time-of-flight spectrum of a single turn is reconstructed using a multi-correlation function of the plural different time-of-flight spectra. The “period of time of ejection of an ion” is generally the amount of time from the point in time when the ion is ejected from an ion source until the point in time when the ion is made to deviate from the loop orbit after passing through this orbit. Hereinafter, this will be simply referred to as the “ion ejection time.” With this method, obtaining a mass spectrum substantially in real time while performing a measurement is almost impossible because of the large amount of computation of the multi-correlation function, which requires a considerable computing time. Further, if the number of peaks appearing on the time-of-flight spectra is significantly large, the amount of computation becomes enormous. In such a case, it is difficult to obtain a result in a practically acceptable length of time if a general-purpose personal computer is used.
Another method for obtaining a mass spectrum is described in WO 2009/075011 (Patent Document 3), Nishiguchi, et al. “Taju Shukai Ion Kougakukei Niyoru Atarashii Taju Shukai Shitsruryo Bunseki Hou,” (“Novel Multi-Turn Mass Spectrometry with Multi-Turn Ion Optical Systems”) Shimadzu Review, vol. 66, Nos. 1 and 2, published on Sep. 30, 2009, and Nishiguchi, et al. “Design of a new multi-turn ion optical system ‘IRIS’ for a time-of-flight mass spectrometer,” J. Mass Spectrum., 44 (2009), p. 594. In this method, a time-of-flight spectrum (zero-turn time-of-flight spectrum) for a target sample is obtained in a linear mode in which ions injected into the apparatus are ejected without closed loop orbit. Then, the number of turns and the time of flight in a multi-turn mode, in which an ion may overtake another ion, are predicted from the time-of-flight of the peaks on the zero-turn time-of-flight spectrum. After that, based on this prediction, time-of-flight segments, whose widths are determined by considering the time spread of peaks, are set on the time-of-flight spectrum in the multi-turn mode. Since peaks included in one segment originate from ions with the same number of turns, the number of turns and the mass-to-charge ratio of all the peaks can be uniquely determined unless the adjacent segments do not overlap each other. Hence, the existence of the overlapping of the segments, which are set on the time-of-flight spectrum in the multi-turn mode, is judged to search for a condition under which the overlapping does not occur and to fix the segment setting. Since this determines the optimum ejection time when ions should be ejected from the loop orbit, a measurement in the multi-turn mode is performed by controlling the timing for switching the gate electrode for ejecting ions based on this optimum ejection time. Then, a mass spectrum is obtained from the time-of-flight spectrum obtained as a result of this measurement.
In this method, the data processing is relatively simple, allowing a general-purpose personal computer to perform the processing substantially in real time. However, this method is disadvantageous in that the mass spectrum cannot be created in the case where the number of peaks to be observed is so large that no condition to avoid the overlapping of the segments can be found. When the sample to be measured is a protein, sugar chain or similar substance, it is anticipated that the segments often overlap. Accordingly, the cases to which this method can be applied are significantly limited. Limiting the range of mass-to-charge ratio of the ions introduced into the loop orbit may be another approach to prevent the segments from overlapping. However, this disadvantageously deteriorates the measurement throughput.
JP-A 2005-116343 (Patent Document 2) discloses a method for deducing the mass-to-charge ratio of a target ion by a process including the steps of: measuring a plurality of time-of-flight spectra of a target sample with different ion ejection times; calculating possible candidates for the mass-to-charge ratio of the target ion by assuming number of turns for each peaks on each of the plurality of time-of-flight spectra; and locating a candidate of the mass-to-charge ratio that has been commonly selected on all of the plurality of time-of-flight spectra.
Also in this method, the required data processing is relatively simple and the processing can be performed substantially in real time with a general-purpose personal computer. Finding the relationship of the peaks between the different time-of-flight spectra is easy for a small number of peaks. However, this relating process becomes complicated when the number of components contained in the sample is large and the number of peaks appearing on the time-of-flight spectra is accordingly large. In addition, if the number of peaks is large, an erroneous deduction of the mass-to-charge ratio could accidentally occur with a higher probability. Further, the peaks originating from ions having different mass-to-charge ratios become more likely to accidentally overlap each other on a time-of-flight spectrum, which prevents accurate deduction of the mass-to-charge ratio.